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PMID: 15809351 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

TGF-beta1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells.

The Journal of experimental medicine ·Vol. 201 ·No. 7 ·2005-04-04 ·Pages 1061-7

Marie JC, Letterio JJ, Gavin M, Rudensky AY

Abstract

Transforming growth factor (TGF)-beta1 is a major pluripotential cytokine with a pronounced immunosuppressive effect and its deficiency results in lethal autoimmunity in mice. However, mechanisms of its immunosuppressive action are not completely understood. Here, we report that TGF-beta1 supports the maintenance of Foxp3 expression, regulatory function, and homeostasis in peripheral CD4(+)CD25(+) regulatory T (T reg) cells, but is not required for their thymic development. We found that in 8-10-d-old TGF-beta1-deficient mice, peripheral, but not thymic, T reg cells are significantly reduced in numbers. Moreover, our experiments suggest that a defect in TGF-beta-mediated signaling in T reg cells is associated with a decrease in Foxp3 expression and suppressor activity. Thus, our results establish an essential link between TGF-beta1 signaling in peripheral T reg cells and T reg cell maintenance in vivo.

MeSH Terms
Animals Blotting, Western CD4-Positive T-Lymphocytes/immunology,metabolism Cells, Cultured DNA-Binding Proteins/metabolism Forkhead Transcription Factors Immune Tolerance/immunology Immunosuppression Therapy Mice Mice, Inbred Strains Receptors, Interleukin-2/metabolism Signal Transduction/immunology Thymus Gland/immunology Transforming Growth Factor beta/immunology,metabolism
Chemicals
DNA-Binding Proteins Forkhead Transcription Factors Foxp3 protein, mouse Receptors, Interleukin-2 Transforming Growth Factor beta
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Marie Julien C
Department of Immunology, University of Washington, Seattle, WA 98195, USA.
Letterio John J
Gavin Marc
Rudensky Alexander Y
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20042276
Published
2005-04-04
Pages
1061-7
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2213134
Subset
IM
Grants
NIAID NIH HHS · R01 AI061816 · United States
NIAID NIH HHS · R37 AI034206 · United States
NIAID NIH HHS · R01 AI034206 · United States
NIAID NIH HHS · AI061816 · United States
NIAID NIH HHS · AI34206 · United States
External Links
PubMed source DOI: 10.1084/jem.20042276 PMC Full Text View journal details
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